Most, if not all pathogens, destroy their host cell during pathogen replication. Death of living cells can follow more than one possible scenario. It may result from an external injury, from cell killing during acute infection with cytopathic pathogens, or it may be the outcome of activating an internal pathway for cell suicide—programmed cell death. Programmed cell death or apoptosis is a controlled process by which unwanted cells are selectively eliminated. Apoptosis is a normal physiological process of eliminating unwanted cells from living organisms during embryonic and adult development, but can also be induced in cells following exposure to a pathogen.
The mechanism by which pathogens cause cell death—either direct killing or indirect—varies with the pathogen and the host cell in question. Controversy surrounds the cause of pathogen-induced cell death in even in the most extensively studied pathogens. For example, in human immunodeficiency virus type 1 (HIV-1)-initiated killing of CD4+ cells T cell death has been reported to be caused by syncytium formation-interaction of the envelope glycoprotein (gp120) with CD4 and subsequent fusion of the cells; influenced by type 1/type 2 cytokine modulation; mediated by specific cell death proteases (caspases) that function in the distal portions of the proteolytic cascades involved in apoptosis; membrane tumor necrosis factor induced cooperative signaling of tumor necrosis factor membrane receptors p55 and p75; Fas-induced apoptosis; and direct interaction of HIV gp120 envelop with the T cell CD4 molecule. Although agreement in the mechanism of cell death is disputed, it is clear that pathogen replication results in host cell destruction.
Pathogens replication can only occur inside host cells, commandeering the cell's machinery to reproduce. Infection typically begins when a pathogen encounters a cell with a specific cellular surface receptor molecule that matches the proteins found on the virus. The membranes of the virus and the cell will fuse, followed by release of viral nucleic acids, proteins and enzymes into the cell. Cell-to-cell spread of the pathogen also can occur through the fusion of an infected cell with an uninfected cell. The pathogen nucleic acid moves to the cell nucleus, where in most cases is spliced into the host DNA (for RNA-based pathogens, pathogen encoded reverse transcriptase converts RNA into DNA). Once incorporated into the cellular genome, RNA copies are made that are read by the host cell protein-malcing machinery. After the MRNA is processed in the cell nucleus, it is transported to the cytoplasm. The pathogen co-opts the cellular protein-making machinery to make long chains of viral proteins and enzymes, using the pathogen MRNA as a template. Newly made pathogen proteins, enzymes and nucleic acids gather inside the cell, while the pathogen envelope proteins aggregate within cellular membranes. An immature viral particle forms and pinches off from cellular membranes, acquiring an envelope. Depending on the pathogen, the mature virus particle is either released into the cytoplasm of the cell or released external to the cell.
In the case of HIV-1, the outer coat of the virus, known as the viral envelope, is composed of 72 copies (on average) of a complex HIV protein that protrudes from the envelope surface. This protein, known as Env, consists of a cap made of three or four molecules called glycoprotein (gp) 120, and a stem consisting of three or four gp41 molecules that anchor the structure in the viral envelope. Within the envelope of a mature HIV particle is a bullet-shaped core or capsid, made of 2,000 copies of another viral protein, p24. The capsid surrounds two single strands of HIV RNA, each of which has a copy of the virus genes—nine genes in total. Three of these, gag, pol and env, contain information needed to make structural proteins for new virus particles. The env gene, for example, codes for a protein called gp160 that is broken down by a viral enzyme to form gpl20 and gp41, the components of Env. Three regulatory genes, tat, rev and nef, and three auxiliary genes, vif, vpr and vpu, contain information necessary for the production of proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease. The core of HIV also includes a protein called p7, the HIV nucleocapsid protein; and three enzymes that carry out later steps in the virus life cycle: reverse transcriptase, integrase and protease. Another HIV protein called p17, or the HIV matrix protein, lies between the viral core and the viral envelope.
The ability to either molecularly clone and subsequently express a gene by recombinant technology, isolate whole pathogens, or purify specific pathogen gene(s), has led to the development of sensitive assay systems for detecting pathogens and for measuring immune responses to their infection. Because early pathogen infection often causes no symptoms, a doctor or other health care worker relies on testing a person's blood for the presence of antibodies (disease-fighting proteins) to the pathogen in question for diagnosis. By early testing, treatment at a time when the individuals' immune systems are most able to combat the pathogen and thus prevent the spread the virus to others could occur. Medical diagnose of pathogen's infection is normally performed by using two different types of antibody tests, ELISA and Western Blot. Diagnostic studies with a number of pathogens show that pathogen burden predicts disease progression. That is, people with high levels of pathogen in their bloodstream are more likely to develop pathogen-related symptoms or to die than individuals with lower levels of pathogen. Methods are available to detect specific antigens or nucleic acid sequences. These techniques can detect pathogen exposures that occur before antibody responses are established. Diagnostic detection for most pathogens exist in first-, second-, and third-line screening procedures and the use of Western Blot analysis is routinely established as a recognized confirmatory method.